Here we report a new site-specific conjugation strategy to modify proteins via thiazolidine ligation. Proteins harbouring a 1,2-aminothiol moiety introduced by amber codon suppression technology could be modified chemoselectively with aldehyde-functionalized reagents, such as a biotin-labeled peptide or ubiquitin, under mild conditions to yield homogeneous biotinylated or ubiquitinated products.

Ambient ionization MS has become very popular in analytical science and has now evolved as an effective analytical tool in metabolomics, biological tissue imaging, protein and small molecule drug analysis, where biological samples are probed in a rapid and direct fashion with minimal sample preparation at ambient conditions. However, certain inherent challenges continue to hinder the vibrant prospects of these methods for in situ analyses or to replace conventional methods in bioanalysis. This review provides an introduction to the field and its application in bioanalysis, with an emphasis on the most recent developments and applications. Furthermore, ongoing challenges or limitations related to quantitation, sensitivity, selectivity, instrumentation and mass range of these ambient methods will also be discussed.

We report the discovery of ARD-2051 as a potent and orally efficacious androgen receptor (AR) proteolysis-targeting chimera degrader. ARD-2051 achieves DC 50 values of 0.6 nM and D max >90% in inducing AR protein degradation in both the LNCaP and VCaP prostate cancer cell lines, potently and effectively suppresses AR-regulated genes, and inhibits cancer cell growth. ARD-2051 achieves a good oral bioavailability and pharmacokinetic profile in mouse, rat, and dog. A single oral dose of ARD-2051 strongly reduces AR protein and suppresses AR-regulated gene expression in the VCaP xenograft tumor tissue in mice. Oral administration of ARD-2051 effectively inhibits VCaP tumor growth and causes no signs of toxicity in mice. ARD-2051 is a promising AR degrader for advanced preclinical development for the treatment of AR+ human cancers.

The paper spray-MS approach is simple, sensitive and can potentially enable significant reduction of animal use and cost.

Background: Volumetric absorptive microsampling may reduce the blood collection burden associated with therapeutic drug monitoring of immunosuppression to prevent organ transplant rejection. This work describes the development of a laboratory and analytical technique for quantifying tacrolimus and mycophenolic acid (MPA) from the Tasso-M20™ in human whole blood using bead-based impact-assisted extraction. Results: The sampled blood volume was accurate with estimated volumes within <2% of the expected 20 μl. Recovery using impact-assisted extraction was 73–87% for MPA and 100% for tacrolimus and was hematocrit-independent for both analytes. The LC-MS/MS assay is precise and accurate within the acceptance criteria of 15%. Conclusion: The sampling and extraction procedures allowed for accurate quantification of tacrolimus and MPA. Exploration of abuse scenarios identified important education points for patients conducting home-based sample collections in the future.